Linked Life Data

11745712

Source:http://linkedlifedata.com/resource/pubmed/id/11745712

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
10
pubmed:dateCreated
2001-12-17
pubmed:abstractText
Previous in vitro studies evaluating the permeability of enaminones suggested that their blood-brain barrier (BBB) transport might be influenced by the presence of an efflux mechanism. Therefore, transport mechanisms responsible for these anticonvulsants across the BBB were examined. The transport of enaminones (1 x 10(-4) M) were evaluated over 120 min with verapamil (50 microM) and probenecid (100 microM) using bovine brain microvessel endothelial cells (BBMECs) to assess the role of multidrug resistant (MDR) transport proteins [i.e., P-glycoprotein (Pgp) and MDR protein 1 (MRP1)] on efflux, respectively. Uptake studies in the presence and absence of rhodamine 123 (R123; 3.2 and 5.0 microM) were also performed in a Pgp overexpressing cell line, MCF-7/Adr. Select enaminone esters (12.5 mg/kg) were administered intravenously to mdr 1 a/b (+/+), mdr 1 a/b (-/-) knockout and probenecid pretreated mice (20 +/- 5g). Enaminones and R123 were assayed with validated ultraviolet and fluorescence high-performance liquid chromatography methods, respectively. Verapamil and probenecid significantly ( p>0.05) inhibited the transport of select enaminone esters across BBMECs. Two enaminones caused a statistically significant increase in the uptake of R123 in MCF-7/Adr cells. Concentrations of select enaminones in mdr 1 a/b (-/-) mice brains were significantly higher ( p<0.05) compared with those in mdr 1 a/b (+/+) mice brains; however, no differences were observed in probenecid pretreated animals. Taken together, these results strongly suggest that Pgp may influence enaminone transport at the BBB and hence affect epilepsy treatment with these agents.
pubmed:grant
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Oct
pubmed:issn
0022-3549
pubmed:author
pubmed:copyrightInfo
Copyright 2001 Wiley-Liss, Inc. and the American Pharmaceutical Association J Pharm Sci 90:1540-1552, 2001
pubmed:issnType
Print
pubmed:volume
90
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
1540-52
pubmed:dateRevised
2007-11-14
pubmed:meshHeading
pubmed-meshheading:11745712-ATP-Binding Cassette Transporters, pubmed-meshheading:11745712-Aniline Compounds, pubmed-meshheading:11745712-Animals, pubmed-meshheading:11745712-Anticonvulsants, pubmed-meshheading:11745712-Biological Transport, Active, pubmed-meshheading:11745712-Blood-Brain Barrier, pubmed-meshheading:11745712-Brain, pubmed-meshheading:11745712-Capillaries, pubmed-meshheading:11745712-Cattle, pubmed-meshheading:11745712-Cyclohexanones, pubmed-meshheading:11745712-Endothelium, Vascular, pubmed-meshheading:11745712-Humans, pubmed-meshheading:11745712-Injections, Intravenous, pubmed-meshheading:11745712-Male, pubmed-meshheading:11745712-Mice, pubmed-meshheading:11745712-Mice, Knockout, pubmed-meshheading:11745712-Multidrug Resistance-Associated Proteins, pubmed-meshheading:11745712-P-Glycoprotein, pubmed-meshheading:11745712-Probenecid, pubmed-meshheading:11745712-Rhodamine 123, pubmed-meshheading:11745712-Tissue Distribution, pubmed-meshheading:11745712-Tumor Cells, Cultured, pubmed-meshheading:11745712-Verapamil
pubmed:year
2001
pubmed:articleTitle
Influence of multidrug resistance (MDR) proteins at the blood-brain barrier on the transport and brain distribution of enaminone anticonvulsants.
pubmed:affiliation
Pharmacokinetics Biopharmaceutics Laboratory, Department of Pharmaceutical Science, School of Pharmacy, University of Maryland, 100 Penn Street, AHB, Baltimore, Maryland 21201, USA.
pubmed:publicationType
Journal Article, Comparative Study, Research Support, U.S. Gov't, P.H.S.